Abstract
Background: Disulfide-linked oligodeoxyribonucleotide (ODN) liposomes were formulated and evaluated for the delivery of antisense ODN G3139 in KB human oral carcinoma cells. Materials and Methods: Liposomes composed of 1,2-di-(9Z-octadecenoyl)-3-trimethylammo-nium-propane(DOTAP)/egg phosphatidylcholine/α-tocopheryl polyethylene glycol 1000 succinate were incorporated with hydrophobized disulfide-linked ODN. Disulfide-linked ODN liposomes were characterized for their size, ODN intracellular delivery, Bcl-2 mRNA and protein expression, growth inhibition, and chemosensitization. Results: Intracellular delivery of ODN with disulfide-linked ODN liposomes was more efficient than that with non-liposomal hydrophobized disulfide-linked ODN. Treatment of the cells with disulfide-linked ODN liposomes resulted in efficient Bcl-2 down-regulation greater than that with hydrophobized disulfide-linked ODN and consistent with that of cellular growth inhibition and the sensitization to daunorubicin in KB cells. Disulfide-linked ODN liposomes exhibited superior colloidal stability during 5-week storage. Conclusion: Disulfide-linked liposomes are effective delivery vehicles for antisense ODN.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 31-38 |
| Number of pages | 8 |
| Journal | Anticancer Research |
| Volume | 30 |
| Issue number | 1 |
| State | Published - Jan 2010 |
Keywords
- Antisense oligonucleotide
- Bcl-2
- Disulfide
- Drug delivery
- G3139
- Liposomes